How Advances in Hematologic Oncology Are Influencing Treatment for CLL

Chronic lymphocytic leukemia (CLL) is a leukaemia composed of abnormal B lymphocytes. These cancer cells tend to accumulate in the blood, bone marrow, lymph nodes, spleen, and other organs, and although the disease has an indolent course, and often does not cause symptoms in the early stages after diagnosis, it can eventually transform to a more aggressive phase and may need to be treated.

The improvements in the field of hemato-oncology which have taken place in recent years enable a greater understanding of CLL as well as of individual cases of CLL, enabling more individualized diagnostic, monitoring and treatment approaches based on the disease, molecular characteristics, previous treatment as well as on patient’s general health and treatment preferences.

Understanding When CLL Treatment Is Needed

However, most people with an early stage, asymptomatic CLL may not need to start treatment immediately. In these cases, patients are managed with active surveillance or ‘watch and wait’ as it is also called.

During the period of active surveillance, the oncologist continues to follow the patient’s blood values, size of lymph nodes and spleen, symptoms and in general the patient’s state of health. Only when the CLL starts to cause active CLL-related symptoms or complications does the patient require CLL treatment.

The need for treatment can arise because of CLL-induced symptoms and/or complications. These include deteriorating anemia and/or thrombocytopenia; progressive lymph node/splenomegaly, persistent/intermittent fever, night sweats, unexplained weight loss, and fatigue of increasing severity. An increase in the number of lymphocytes may be one factor to consider when assessing the degree of CLL illness but an increase in the number of lymphocytes alone does not necessarily mean that treatment is indicated.

The Changing Role of Targeted Therapies

Targeted therapies in hematologic oncology are now commonly used to treat patients with CLL. Instead of acting on rapidly dividing cells in general, CLL targeted therapies are designed to specifically inhibit key proteins that CLL cancer cells use for their survival and proliferation.

There are several BTK inhibitors available, such as Zanubrutinib, ibrutinib, and acalabrutinib. These work by specifically inhibiting the Bruton’s tyrosine kinase (BTK), a protein essential for the B-cell receptor signaling pathway. Inhibiting BTK prevents signaling that allows CLL cells to survive and proliferate.

Another approach to fight CLL is BCL-2 inhibitors. The most used of this class of drugs is venetoclax. It targets the BCL-2 protein that is overexpressed in CLL cells to prevent their apoptosis or programmed cell death. These approaches have expanded available treatment options for CLL and may be considered as alternatives to conventional chemotherapy for some patients based on various factors.

Molecular Testing and Personalized Care

More recently, a greater emphasis has been placed on the molecular pathology of CLL. The results from genetic/molecular tests can help the managing physician get a better sense and understanding of the disease and, accordingly, manage the patient better.

Some tests are useful to know about the biology of CLL in terms of its risk and behavior. These tests include assessment of TP53 mutations, 17p deletion and IGHV mutation status.

The molecular findings from blood tests are considered in conjunction with clinical features such as symptoms, extent of reduction in blood counts, rate of disease progression, prior treatment(s), presence of co-existing medical conditions and patient’s general health. This information is then considered in conjunction with clinical information to guide an individualized approach for the management of CLL.

Combination and Time-Limited Treatment

In onco-hematology, by targeting single proteins in CLL, new drugs can also be combined to reach deeper remissions in selected patients. Some CLL treatments are intended to be given for a set period rather than on-going and some patients may see benefit from treatments being given for a set period in between periods of no treatment.

Examples of regimens using venetoclax in combination with other therapies have been used in a time-limited manner for selected patients. There are many factors that need to be considered when weighing up a time-limited approach versus continued therapy including the disease itself, previous treatment(s), potential toxicity of the regimen, drug interactions, the monitoring burden and side effects as well as patient preference.

Safety and Monitoring Treatment

Monitoring in CLL for most treatments is standard practice, as treatments in general have both positive and negative effects. This is particularly the case for targeted therapies, which are intended to specifically act on cancer cells.

Patients on treatment for CLL require close monitoring, especially those on treatments that have known side effects and toxicities. Hematologic monitoring, for example, assessment of blood pressure, cardiac function, renal function and liver function may be required. In addition, the degree to which a patient’s CLL affects the immune system can increase the risk of infection.

However, another potential complication, tumor lysis syndrome, may require close monitoring, particularly at initiation of therapy, by gradual dose escalation and close monitoring of affected parameters. Regular checks enable health care providers to identify any problems that can occur during or after treatment and to treat any side effects with appropriate support and/or treatment.

The Importance of Previous Treatment

Looking at a patient’s previous treatment helps establish a good basis for the current situation. Sometimes different treatments are available to patients who are receiving treatment for the first time compared to patients with relapsed CLL that is refractory to previous therapy.

Previous treatment and the duration of time it controlled CLL, the CLL’s behavior since last treatment, and CLL molecular characteristics that have developed or changed since last treatment, are all considered. This helps when deciding on subsequent treatment(s) and how they should be sequenced.

Considering the Patient as a Whole

Hematologic oncology has evolved towards patient-centered decision making. CLL can affect patients differently, and individual patients have different co-morbidities, other medical treatments, drug interactions, potential treatment toxicities and require different treatment goals.

Factors including other medical conditions, current medications, potential drug interactions, potential treatment side effects, duration of treatment, requirement for ongoing monitoring and impact on quality of life are considered. The patient’s preference for a time-limited or continuous treatment approach must also be considered, with the description of potential benefits and risks to patients by the healthcare team.

Supportive Care and Long-Term Management

Looking at CLL from a Hematologic Oncology perspective makes it clear that managing the disease to ensure long-term health is important. This includes monitoring for infection, managing side effects from treatment and overall management of the patient’s health.

Therefore, it is crucial for CLL patients to inform their doctors about any new or worsening symptoms and to attend all scheduled follow-up appointments. By following those measures and taking measures to prevent complications, by getting vaccinated if necessary and keeping an eye on their health, CLL patients may benefit from appropriate supportive care. As CLL is a chronic condition, treatment strategies may change over time and are typically reassessed regularly to determine whether the current treatment approach remains appropriate for the individual patient.

Looking Towards the Future

There is ongoing research in hematologic oncology for new targeted drugs, combination therapies, different treatment sequences and new approaches to disease management for improved disease control and side effects management. The intent of continued hematology and oncology research is to better utilize current treatments as well as to develop new ones to control CLL in individual patients.

New therapies for CLL are being investigated, including targeted treatments and approaches intended to manage treatment-related side effects. Clinical research aims to determine how they may be used in different patient populations, considering disease characteristics and coexisting medical conditions.

Medical Disclaimer: The information provided in this article is intended for educational purposes only and should not be interpreted as medical advice, clinical guidelines, or a recommendation for any specific treatment.